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Advanced liver function assessment in patients with intestinal failure on long-term parenteral nutrition.

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BACKGROUND & AIMS: Intestinal failure associated liver disease (IFALD) is one of the leading complications and causes of deaths in adult patients receiving home parenteral nutrition for chronic … intestinal failure (CIF). Early diagnosis of IFALD is key to alleviate the progression of hepatic dysfunction. The aim of this study was to evaluate the capability of noninvasive liver function tests. METHODS: 90 adult patients with CIF receiving long-term home parenteral nutrition were included in a prospective cross-sectional study at our department between 2014 and 2017. All participants underwent dynamic liver function assessment (maximum liver function capacity [LiMAx] test, indocyanine green [ICG] test), transient elastography (FibroScan), blood tests and comprehensive nutritional status assessment. Univariate and multivariable analysis were performed to identify predictors of liver function. RESULTS: LiMAx, ICG test, and FibroScan highly correlated with standard liver function tests. Multivariable analysis identified intact ileum (B = 520.895; p = 0.010), digestive anatomy type 3 (B = 75.612; p = 0.025), citrulline level (B = 3.428; p = 0.040), parenteral olive oil intake (B = -0.570; p = 0.043), and oral intake (B = 182.227; p = 0.040) as independent risk factors affecting liver function determined by LiMAx test. ICG test and FibroScan showed no correlation with gastrointestinal and nutrition-related parameters. CONCLUSION: The LiMAx test is significantly associated with widely accepted risk factors for IFALD by multivariable analysis, whereas ICG test and FibroScan failed to show significant correlations. Liver function assessment by LiMAx test may therefore have the potential to detect alterations in liver function and identify patients at risk for the development of IFALD. Longitudinal studies are needed to investigate the impact of liver function determined by LiMAx test on long-term outcome in patients with CIF.

Authors: E. Bluthner, J. Bednarsch, U. F. Pape, M. Karber, S. Maasberg, U. A. Gerlach, A. Pascher, B. Wiedenmann, J. Pratschke, M. Stockmann

Date Published: 20th Mar 2019

Publication Type: Not specified

Hepatic CYP1A2 activity in liver tumors and the implications for preoperative volume-function analysis.

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Dynamic liver function assessment by the (13)C-methacetin maximal liver function capacity (LiMAx) test reflects the overall hepatic CYP1A2 activity. One proven strategy for preoperative risk assessement … in liver surgery includes the combined assessment of the dynamic liver function by the LiMAx test, the volumetric analysis of the liver and calculation of future liver remnant function. This so-called volume-function analysis assumes that the remaining CYP1A2 activity in any tumor lesion is zero. The here presented study aims to assess the remaining CYP1A2 activities in different hepatic tumor lesions and its consequences for the preoperative volume-function analysis in patients undergoing liver surgery. The CYP1A2 activity analysis of neoplastic lesions and adjacent non-tumor liver tissue from resected tumor specimens revealed a significantly higher CYP1A2 activity (median, interquartile range) in non-tumor tissues (35.5, 15.9-54.4 microU/mg) as compared to hepatocellular adenomas (7.35, 1.2-32.5 microU/mg), hepatocellular carcinomas (0.18, 0.0-2.0 microU/mg) or colorectal liver metastasis (0.17, 0.0-2.1 microU/mg), respectively. In non-tumor liver tissue a gradual decline in CYP1A2 activity with exacerbating fibrosis was observed. The CYP1A2 activity differences were also reflected in CYP1A2 protein signals in the assessed hepatic tissues. Volume-function analysis showed a minimal deviation compared to the current standard calculation for hepatocellular carcinomas or colorectal liver metastasis (<1% difference), while a difference of 11.9% was observed for hepatocellular adenomas. These findings are important for a refined preoperative volume-function analysis and improved surgical risk assessment in hepatocellular adenoma cases with low LiMAx values.

Authors: T. Wuensch, N. Heucke, J. Wizenty, J. Quint, B. Sinn, R. Arsenic, M. Jara, M. Kaffarnik, J. Pratschke, M. Stockmann

Date Published: 14th Mar 2019

Publication Type: Not specified

Non-invasive structure-function assessment of the liver by 2D time-harmonic elastography and the dynamic Liver MAximum capacity (LiMAx) test.

Abstract (Expand)

BACKGROUND AND AIM: Accurate assessment of structural and functional characteristics of the liver could improve the diagnosis and the clinical management of patients with chronic liver diseases. However, … the structure-function relationship in the progression of chronic liver disease remains elusive. The aim of this study is the combined measurement of liver function by the (13) C-methacetin Liver MAximum capacity (LiMAx) test and tissue-structure related stiffness by 2D time-harmonic elastography for the assessment of liver disease progression. METHODS: LiMAx test and time-harmonic elastography were applied, and the serological scores fibrosis 4 index and aspartate aminotransferase to platelet ratio index were calculated in patients with chronic liver diseases (n = 75) and healthy control subjects (n = 22). In 47 patients who underwent surgery, fibrosis was graded by histological examination of the resected liver tissue. RESULTS: LiMAx values correlated negatively with liver stiffness (r = -0.747), aminotransferase to platelet ratio index (r = -0.604), and fibrosis 4 (r = -0.573). Median (interquartile range) LiMAx values decreased with fibrosis progression from 395 mug/kg/h (371-460 mug/kg/h) in participants with no fibrosis to 173 mug/kg/h (126-309 mug/kg/h) in patients with severe fibrosis. Median liver stiffness increased progressively with the stage of fibrosis from no fibrosis (1.56 m/s [1.52-1.63 m/s]) to moderate fibrosis (1.60 m/s [1.54-1.67 m/s]) to severe fibrosis (1.85 m/s [1.76-1.92 m/s]). CONCLUSION: Our findings show that structural changes in the liver due to progressing liver diseases and reflected by increased tissue stiffness correlate with a functional decline of the organ as reflected by a decreased metabolic capacity of the liver.

Authors: N. Heucke, T. Wuensch, J. Mohr, M. Kaffarnik, R. Arsenic, B. Sinn, T. Muller, J. Pratschke, M. Stockmann, I. Sack, H. Tzschatzsch

Date Published: 13th Feb 2019

Publication Type: Not specified

The predictive value of future liver remnant function after liver resection for HCC in noncirrhotic and cirrhotic patients.

Abstract (Expand)

BACKGROUND: Surgical procedures in patients with underlying liver disease are still burdened by a high rate of postoperative morbidity, especially posthepatectomy liver failure (PHLF), ranging from 1.2 … to 33.8%. The aim of this study was to investigate the prognostic value of volume/function analysis for the prediction of hepatectomy-related morbidity in patients with hepatocellular carcinoma. METHODS: Clinicopathological data were analysed in 261 patients who underwent liver resection for HCC between 2001 and 2014. Future liver remnant volume (FLRV) and future liver remnant function (FLRF) based on LiMAx test were obtained retrospectively. A subgroup analysis for high-risk patients with impaired liver function was conducted. Univariate and multivariate regression analysis was performed to identify risk factors for major complications, defined by Dindo >/= IIIb and PHLF grade >/= B. RESULTS: In the total cohort, FLRF was independently associated with major complications. FLRV, resected liver volume, and FLRF were independent risk factors for PHLF. In a subgroup analysis of high-risk patients, FLRF was identified as the only independent risk factor for major complications and PHLF development. DISCUSSION: These results suggest the superior value of FLRF to FLRV in predicting postoperative complications as well as PHLF in patients with chronic liver disease.

Authors: E. Bluthner, M. Jara, R. Shrestha, W. Faber, J. Pratschke, M. Stockmann, M. Malinowski

Date Published: 9th Feb 2019

Publication Type: Not specified

Dynamic Metabolic Zonation of the Hepatic Glucose Metabolism Is Accomplished by Sinusoidal Plasma Gradients of Nutrients and Hormones.

Abstract (Expand)

Being the central metabolic organ of vertebrates, the liver possesses the largest repertoire of metabolic enzymes among all tissues and organs. Almost all metabolic pathways are resident in the parenchymal … cell, hepatocyte, but the pathway capacities may largely differ depending on the localization of hepatocytes within the liver acinus-a phenomenon that is commonly referred to as metabolic zonation. Metabolic zonation is rather dynamic since gene expression patterns of metabolic enzymes may change in response to nutrition, drugs, hormones and pathological states of the liver (e.g., fibrosis and inflammation). This fact has to be ultimately taken into account in mathematical models aiming at the prediction of metabolic liver functions in different physiological and pathological settings. Here we present a spatially resolved kinetic tissue model of hepatic glucose metabolism which includes zone-specific temporal changes of enzyme abundances which are driven by concentration gradients of nutrients, hormones and oxygen along the hepatic sinusoids. As key modulators of enzyme expression we included oxygen, glucose and the hormones insulin and glucagon which also control enzyme activities by cAMP-dependent reversible phosphorylation. Starting with an initially non-zonated model using plasma profiles under fed, fasted and diabetic conditions, zonal patterns of glycolytic and gluconeogenetic enzymes as well as glucose uptake and release rates are created as an emergent property. We show that mechanisms controlling the adaptation of enzyme abundances to varying external conditions necessarily lead to the zonation of hepatic carbohydrate metabolism. To the best of our knowledge, this is the first kinetic tissue model which takes into account in a semi-mechanistic way all relevant levels of enzyme regulation.

Authors: N. Berndt, H. G. Holzhutter

Date Published: 12th Jan 2019

Publication Type: Journal

Prospective Assessment of Liver Function by an Enzymatic Liver Function Test to Estimate Short-Term Survival in Patients with Liver Cirrhosis.

Abstract (Expand)

BACKGROUND: MELD attempts to objectively predict the risk of mortality of patients with liver cirrhosis and is commonly used to prioritize organ allocation. Despite the usefulness of the MELD, updated … metrics could further improve the accuracy of estimates of survival. AIMS: To assess and compare the prognostic ability of an enzymatic (13)C-based liver function test (LiMAx) and distinct markers of liver function to predict 3-month mortality of patients with chronic liver failure. METHODS: We prospectively investigated liver function of 268 chronic liver failure patients without hepatocellular carcinoma. Primary study endpoint was liver-related death within 3 months of follow-up. Prognostic values were calculated using Cox proportional hazards and logistic regression analysis. RESULTS: The Cox proportional hazard model indicated that LiMAx (p < 0.001) and serum creatinine values (p < 0.001) were the significant parameters independently associated with the risk of liver failure-related death. Logistic regression analysis revealed LiMAx and serum creatinine to be independent predictors of mortality. Areas under the receiver-operating characteristic curves for MELD (0.86 [0.80-0.92]) and for a combined score of LiMAx and serum creatinine (0.83 [0.76-0.90]) were comparable. CONCLUSIONS: Apart from serum creatinine levels, enzymatic liver function measured by LiMAx was found to be an independent predictor of short-term mortality risk in patients with liver cirrhosis. A risk score combining both determinants allows reliable prediction of short-term prognosis considering actual organ function. Trial Registration Number (German Clinical Trials Register) # DRKS00000614.

Authors: M. Jara, T. Dziodzio, M. Malinowski, K. Luttgert, R. Nikolov, P. V. Ritschl, R. Ollinger, J. Pratschke, M. Stockmann

Date Published: 9th Nov 2018

Publication Type: Not specified

Tomoelastography Paired With T2* Magnetic Resonance Imaging Detects Lupus Nephritis With Normal Renal Function.

Abstract (Expand)

OBJECTIVES: The aim of this study was to test multiparametric magnetic resonance imaging including blood oxygen level-dependent (BOLD) imaging by T2* mapping, magnetic resonance elastography (MRE) by … tomoelastography, and diffusion-weighted imaging (DWI) for detecting nephropathy in patients with lupus nephritis (LN). METHODS: Forty-one subjects (25 patients with LN and 16 age- and sex-matched healthy volunteers; LN: mean age, 47.3 +/- 14.8 years; 22 female subjects; volunteers: mean age, 43.9 +/- 11.6 years; 13 female subjects) were prospectively enrolled. The LN group was further divided into subgroups with normal (LN-nRF, GFR > 90 mL/min per 1.73 m) and compromised renal function (LN-cRF, GFR < 90 mL/min per 1.73 m). All subjects were examined by multifrequency MRE, BOLD imaging, and DWI, yielding shear wave speed (SWS; in meter per second), T2* relaxation times (in millisecond), and apparent diffusion coefficient (ADC; in millimeter square per second), respectively. Renal subregional analysis was performed for the medulla (ME), inner cortex (CoI), and outer cortex (CoO). Imaging markers were correlated to clinical parameters such as GFR and protein-to-urine creatinine ratio. Cutoffs and area under the receiver operating curve (AUROC) were computed to test diagnostic performances. RESULTS: Compared with CoI and CoO, LN-nRF predominantly affects ME tissue (SWS: -7%, P < 0.01; T2*: +9%, P < 0.05; ADC: -5%, P = 0.27). Detection of LN-nRF was better with MRE compared with BOLD imaging and DWI (AUROC = 0.81, 0.76, not significant), whereas pairing MRE with T2* further increased diagnostic power (AUROC = 0.91). Disease progression was associated with reduction of SWS also in CoI (LN-nRF, 3.04 +/- 0.38 m/s; LN-cRF, 2.60 +/- 0.26 m/s; p = 0.013), allowing distinction of LN-nRF from LN-cRF (AUROC = 0.83). Diffusion-weighted imaging was only sensitive to LN-cRF in ME tissue (ADC, -12%; P < 0.05). CONCLUSIONS: Lupus nephritis with normal renal function first arises in MRE and BOLD images within ME tissue, progressing to CoI tissue once renal function becomes impaired and diffusion of tissue water changes.

Authors: S. R. Marticorena Garcia, M. Grossmann, A. Bruns, M. Durr, H. Tzschatzsch, B. Hamm, J. Braun, I. Sack, J. Guo

Date Published: 18th Sep 2018

Publication Type: Journal

US Time-Harmonic Elastography: Detection of Liver Fibrosis in Adolescents with Extreme Obesity with Nonalcoholic Fatty Liver Disease

Abstract (Expand)

Purpose To measure in vivo liver stiffness by using US time-harmonic elastography in a cohort of pediatric patients who were overweight to extremely obese with nonalcoholic fatty liver disease (NAFLD) … and to evaluate the diagnostic value of time-harmonic elastography for differentiating stages of fibrosis associated with progressive disease. Materials and Methods In this prospective study, 67 consecutive adolescents (age range, 10-17 years; mean body mass index, 34.7 kg/m2; range, 21.4-50.4 kg/m2) with biopsy-proven NAFLD were enrolled. Liver stiffness was measured by using time-harmonic elastography based on externally induced continuous vibrations of 30 Hz to 60 Hz frequency and real-time B-mode-guided wave profile analysis covering tissue depths of up to 14 cm. The diagnostic accuracy of time-harmonic elastography in staging liver fibrosis was assessed with area under the receiver operating characteristic curve (AUC) analysis. Liver stiffness cutoffs for the differentiation of fibrosis stages were identified based on the highest Youden index. Results Time-harmonic elastography was feasible in all patients (0% failure rate), including 70% (n = 47) of individuals with extreme obesity (body mass index above the 99.5th percentile). AUC analysis for the detection of any fibrosis (≥ stage F1), moderate fibrosis (≥ stage F2), and advanced fibrosis (≥ stage F3) was 0.88 (95% confidence interval [CI]: 0.80, 0.96), 0.99 (95% CI: 0.98, 1.00), and 0.88 (95% CI: 0.80, 0.96), respectively. The best liver stiffness cutoffs were 1.52 m/sec for at least stage F1, 1.62 m/sec for at least stage F2, and 1.64 m/sec for at least stage F3. Conclusion US time-harmonic elastography allows accurate detection of moderate fibrosis even in pediatric patients with extreme obesity. Larger clinical trials are warranted to confirm the accuracy of US time-harmonic elastography.

Authors: Christian A. Hudert, Heiko Tzschätzsch, Jing Guo, Birgit Rudolph, Hendrik Bläker, Christoph Loddenkemper, Werner Luck, Hans-Peter Müller, Daniel C. Baumgart, Bernd Hamm, Jürgen Braun, Hermann-Georg Holzhütter, Susanna Wiegand, Ingolf Sack

Date Published: 1st Jul 2018

Publication Type: Not specified

HEPATOKIN1 is a biochemistry-based model of liver metabolism for applications in medicine and pharmacology.

Abstract (Expand)

The epidemic increase of non-alcoholic fatty liver diseases (NAFLD) requires a deeper understanding of the regulatory circuits controlling the response of liver metabolism to nutritional challenges, … medical drugs, and genetic enzyme variants. As in vivo studies of human liver metabolism are encumbered with serious ethical and technical issues, we developed a comprehensive biochemistry-based kinetic model of the central liver metabolism including the regulation of enzyme activities by their reactants, allosteric effectors, and hormone-dependent phosphorylation. The utility of the model for basic research and applications in medicine and pharmacology is illustrated by simulating diurnal variations of the metabolic state of the liver at various perturbations caused by nutritional challenges (alcohol), drugs (valproate), and inherited enzyme disorders (galactosemia). Using proteomics data to scale maximal enzyme activities, the model is used to highlight differences in the metabolic functions of normal hepatocytes and malignant liver cells (adenoma and hepatocellular carcinoma).

Authors: N. Berndt, S. Bulik, I. Wallach, T. Wunsch, M. Konig, M. Stockmann, D. Meierhofer, H. G. Holzhutter

Date Published: 21st Jun 2018

Publication Type: Not specified

The importance of membrane microdomains for bile salt-dependent biliary lipid secretion.

Abstract (Expand)

Alternative models explaining the biliary lipid secretion at the canalicular membrane of hepatocytes exist: successive lipid extraction by preformed bile salt micelles, or budding of membrane fragments … with formation of mixed micelles. To test the feasibility of the latter mechanism, we developed a mathematical model that describes the formation of lipid microdomains in the canalicular membrane. Bile salt monomers intercalate into the external hemileaflet of the canalicular membrane, to form a rim to liquid disordered domain patches that then pinch off to form nanometer-scale mixed micelles. Model simulations perfectly recapitulate the measured dependence of bile salt-dependent biliary lipid extraction rates upon modulation of the membrane cholesterol (lack or overexpression of the cholesterol transporter Abcg5-Abcg8) and phosphatidylcholine (lack of Mdr2, also known as Abcb4) content. The model reveals a strong dependence of the biliary secretion rate on the protein density of the membrane. Taken together, the proposed model is consistent with crucial experimental findings in the field and provides a consistent explanation of the central molecular processes involved in bile formation.

Authors: J. Eckstein, H. G. Holzhutter, N. Berndt

Date Published: 1st Mar 2018

Publication Type: Not specified

Full-Field-of-View Time-Harmonic Elastography of the Native Kidney.

Abstract (Expand)

The purpose of this study was to analyze full-field-of-view maps of renal shear wave speed (SWS) measured by time-harmonic elastography (THE) in healthy volunteers in terms of reproducibility, regional … variation and physiologic effects. The kidneys of 37 healthy volunteers were investigated by multifrequency THE. The complete renal parenchyma, as well as cortex and medulla, was analyzed. A subgroup was investigated to test reproducibility (n = 3). Significant differences between SWS in cortex, medulla and full parenchyma were observed (2.10 +/- 0.17, 1.35 +/- 0.11 and 1.71 +/- 0.16 m/s, all p values < 0.001) with mean intra-volunteer standard deviations of repeated measurements of 0.04 m/s (1.6%), 0.06 m/s (4.0%) and 0.08 m/s (4.5%), respectively. No effects of kidney anatomy, age, body mass index, blood pressure and heart rate on SWS were observed. THE allows generation of full-field-of-view SWS maps of native kidneys with high reproducibility.

Authors: S. R. Marticorena Garcia, M. Grossmann, S. T. Lang, M. Nguyen Trong, M. Schultz, J. Guo, B. Hamm, J. Braun, I. Sack, H. Tzschatzsch

Date Published: 27th Feb 2018

Publication Type: Not specified

A multiscale modelling approach to assess the impact of metabolic zonation and microperfusion on the hepatic carbohydrate metabolism.

Abstract (Expand)

The capacity of the liver to convert the metabolic input received from the incoming portal and arterial blood into the metabolic output of the outgoing venous blood has three major determinants: The … intra-hepatic blood flow, the transport of metabolites between blood vessels (sinusoids) and hepatocytes and the metabolic capacity of hepatocytes. These determinants are not constant across the organ: Even in the normal organ, but much more pronounced in the fibrotic and cirrhotic liver, regional variability of the capillary blood pressure, tissue architecture and the expression level of metabolic enzymes (zonation) have been reported. Understanding how this variability may affect the regional metabolic capacity of the liver is important for the interpretation of functional liver tests and planning of pharmacological and surgical interventions. Here we present a mathematical model of the sinusoidal tissue unit (STU) that is composed of a single sinusoid surrounded by the space of Disse and a monolayer of hepatocytes. The total metabolic output of the liver (arterio-venous glucose difference) is obtained by integration across the metabolic output of a representative number of STUs. Application of the model to the hepatic glucose metabolism provided the following insights: (i) At portal glucose concentrations between 6-8 mM, an intra-sinusoidal glucose cycle may occur which is constituted by glucose producing periportal hepatocytes and glucose consuming pericentral hepatocytes, (ii) Regional variability of hepatic blood flow is higher than the corresponding regional variability of the metabolic output, (iii) a spatially resolved metabolic functiogram of the liver is constructed. Variations of tissue parameters are equally important as variations of enzyme activities for the control of the arterio-venous glucose difference.

Authors: N. Berndt, M. S. Horger, S. Bulik, H. G. Holzhutter

Date Published: 16th Feb 2018

Publication Type: Not specified

Genetic determinants of steatosis and fibrosis progression in pediatric non-alcoholic fatty liver disease.

Abstract (Expand)

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adolescents today. In comparison to adult disease, pediatric NAFLD may show a … periportal localization, which is associated with advanced fibrosis. This study aimed to assess the role of genetic risk variants for histologic disease pattern and severity in childhood NAFLD. METHODS: We studied 14 single nucleotide polymorphisms (SNP) in a cohort of 70 adolescents with biopsy-proven NAFLD. Genotype was compared to an adult control cohort (n=200) and analyzed in relation to histologic disease severity and liver tissue proteomics. RESULTS: Three of the 14 SNPs were significantly associated with pediatric NAFLD after FDR adjustment, rs738409 (PNPLA3, P=2.80x10(-06) ), rs1044498 (ENPP1, P=0.0091) and rs780094 (GCKR, P=0.0281). The severity of steatosis was critically associated with rs738409 (OR=3.25; 95% CI: 1.72-6.52, FDR adjusted P=0.0070). The strongest variants associated with severity of fibrosis were rs1260326, rs780094 (both GCKR) and rs659366 (UCP2). PNPLA3 was associated with a portal pattern of steatosis, inflammation and fibrosis. Proteome profiling revealed decreasing levels of GCKR protein with increasing carriage of the rs1260326/rs780094 minor alleles and down-regulation of the retinol pathway in rs738409 G/G carriers. Computational metabolic modelling highlighted functional relevance of PNPLA3, GCKR and UCP2 for NAFLD development. CONCLUSIONS: This study provides evidence for the role of PNPLA3 as a determinant of portal NAFLD localization and severity of portal fibrosis in children and adolescents, the risk variant being associated with an impaired hepatic retinol metabolism. This article is protected by copyright. All rights reserved.

Authors: C. A. Hudert, S. Selinski, B. Rudolph, H. Blaker, C. Loddenkemper, R. Thielhorn, N. Berndt, K. Golka, C. Cadenas, J. Reinders, S. Henning, P. Bufler, P. L. M. Jansen, H. G. Holzhutter, D. Meierhofer, J. G. Hengstler, S. Wiegand

Date Published: 18th Jan 2018

Publication Type: Not specified

Renal oncocytoma characterized by the defective complex I of the respiratory chain boosts the synthesis of the ROS scavenger glutathione.

Abstract (Expand)

Renal oncocytomas are rare benign tumors of the kidney and characterized by a deficient complex I (CI) enzyme activity of the oxidative phosphorylation (OXPHOS) system caused by mitochondrial DNA (mtDNA) … mutations. Yet, little is known about the underlying molecular mechanisms and alterations of metabolic pathways in this tumor. We compared renal oncocytomas with adjacent matched normal kidney tissues on a global scale by multi-omics approaches, including whole exome sequencing (WES), proteomics, metabolomics, and metabolic pathway simulation. The abundance of proteins localized to mitochondria increased more than 2-fold, the only exception was a strong decrease in the abundance for CI subunits that revealed several pathogenic heteroplasmic mtDNA mutations by WES. We also observed renal oncocytomas to dysregulate main metabolic pathways, shunting away from gluconeogenesis and lipid metabolism. Nevertheless, the abundance of energy carrier molecules such as NAD(+), NADH, NADP, ATP, and ADP were significantly higher in renal oncocytomas. Finally, a substantial 5000-fold increase of the reactive oxygen species scavenger glutathione can be regarded as a new hallmark of renal oncocytoma. Our findings demonstrate that renal oncocytomas undergo a metabolic switch to eliminate ATP consuming processes to ensure a sufficient energy supply for the tumor.

Authors: G. Kurschner, Q. Zhang, R. Clima, Y. Xiao, J. F. Busch, E. Kilic, K. Jung, N. Berndt, S. Bulik, H. G. Holzhutter, G. Gasparre, M. Attimonelli, M. Babu, D. Meierhofer

Date Published: 1st Dec 2017

Publication Type: Not specified

Tomoelastography of the native kidney: Regional variation and physiological effects on in vivo renal stiffness.

Abstract (Expand)

PURPOSE: To measure normal renal stiffness in adults, taking into account regional variation, hydration, and urinary status. METHODS: Thirty-six healthy volunteers were examined by tomoelastography … based on MR elastography at four frequencies, from 40 to 70 Hz and multifrequency shear wave speed recovery. Regional wave speeds were derived for the medulla, cortex (inner cortex and outer cortex), and renal pelvis, and examined for age-related effects. Subgroups were repeatedly examined for reproducibility, amount of prior water drinking, and urinary status. Variations in renal perfusion were simulated ex vivo using a porcine kidney subjected to venous water inflow at different pressures. RESULTS: Shear wave speed (stiffness) of renal parenchyma was 2.46 +/- 0.12 m/s (inner cortex: 2.91 +/- 0.17 m/s; outer cortex: 2.52 +/- 0.11 m/s; medulla: 2.15 +/- 0.08 m/s) without side differences and a tendency toward softening with age (P = 0.028). Corresponding intraclass correlation for reproducibility coefficients were 0.78 (inner cortex: 0.80; outer cortex: 0.81; medulla: 0.80). Water drinking resulted in slightly higher values in inner cortex and lower values in medulla (both P = 0.039), which was consistent with the results in perfused specimens. A full bladder led to higher renal pelvis stiffness (P = 0.004), whereas renal parenchyma remained uninfluenced. Stiffness of the porcine renal cortex increased with venous inflow pressure, whereas medulla stiffness decreased. CONCLUSIONS: Tomoelastography provides full field of view maps of renal stiffness with highly detailed resolution and sensitivity to physiological effects related to age and fluid-solid tissue interactions. These basic data could be used to compare pathological conditions in the future. Magn Reson Med, 2017. (c) 2017 International Society for Magnetic Resonance in Medicine.

Authors: S. R. Marticorena Garcia, M. Grossmann, S. T. Lang, H. Tzschatzsch, F. Dittmann, B. Hamm, J. Braun, J. Guo, I. Sack

Date Published: 30th Aug 2017

Publication Type: Not specified

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